[HN Gopher] New CRISPR-based map ties every human gene to its fu... ___________________________________________________________________ New CRISPR-based map ties every human gene to its function Author : gumby Score : 315 points Date : 2022-06-10 15:54 UTC (7 hours ago) (HTM) web link (news.mit.edu) (TXT) w3m dump (news.mit.edu) | loxias wrote: | > New CRISPR-based map ties every human gene to its function | | The title would be so much better if s/its/a/. | | There is no way we'll have an operative map from "all" genes to | function anytime soon. Sometimes hundreds of genes work together, | interact with other microbiomes we contain or our environment to | produce what might seem to be a "simple" quality like height. | achenet wrote: | There's an interview with Ken Thompson from about 2008 where he | says that most of the work in CS has already been done, and he's | advising his son to go into biology. | | I feel like CRISPR is the transistor of the 21st century. | dekhn wrote: | CRISPR is more like a machine to make large-node-size | integrated circuits. Somebody else has to design the circuit, | make it manufacturable, and integrate the circuit with a whole | bunch of other hardware. | | I work in biotech at a company that is one of the few golden | geese that lays 2-3 successful drugs with no competitors every | few years. I have 30+ years of experience (deep experience) in | machine learning, biology, and computer science. | | We are so far behind where we could be, in terms of turning | biology into technology, that's almost shameful. Every day I | see another system that says it can generate 10 times the data | of the previous machine, but the actual amount of knowledge we | are extracting for all that data collection is growing | logarithmically. This is because for a long time biology has | greatly underfunded computing and data. | | The one great shining light is AlphaFold. AF2 finally | demonstrated to a wide range of scientists across many domains | that a really great team using techniques that are barely known | outside of FAAMG can work with some long-term experts to move a | metric (quality of predicted protein structures compared to | golden data) substantially further and faster than even the | most wildly optimistic predicted. Not only that, some of the | techniques they used didn't even exist several years ago | (transformers, jax, various graph learning systems), and the | work was replicated externally once the leading academic team | had a hint of the direction to go in. | | To me, nothing about what I said is surprising to me; I | predicted these outcomes a long time ago. Most of the reasons | that it comes slower than it could are combinations of culture, | incentive, morals/ethics, politics, innovator's dilemmas and a | hundred different bottlenecks. Recently, the challenge has been | that most of the really smart computational biologists | disappear into FAAMG and don't contribute back the things they | learn there to research. | | We're all waiting for that next moment when the cross product | of Genentech and Isomorphic Labs announces that they have a | computational model that can do end to end prediction of drug, | from initial disease target to FDA approval post-phase III | trial. That's been the dream for some time but we're nowhere | near it still, and it remains to be seen whether some group can | conjure all the necessary bits to solve the remaining | underlying problems associated with that "far beyond NP-hard | problem" | Invictus0 wrote: | AI? | JKCalhoun wrote: | Perhaps also future biology? | jazzyjackson wrote: | I'm still holding out for photonics and other optical-analog | computers (where are my instantaneous trig co-processors?) but | that does sound like good advice | foobiekr wrote: | The problem with this is that biology will likely end up | dominated by China due to a willingness to conduct experiments | that are otherwise non-viable in most countries. | jeffreyrogers wrote: | There's still so much basic research to be done that I doubt | this will be a limiting factor for a while. | ornornor wrote: | > non-viable | | Did you mean unethical or are you talking about something | else? | mod wrote: | Forbidden by law or fear of backlash (often due to ethical | implications) | jarenmf wrote: | Yeah, it feels like most fields are stagnated except for | biology and neuroscience. I am a postdoc right now but have | considered seriously switching fields to work on something | exciting. | PartiallyTyped wrote: | I fail to see how CS has stagnated since 2008, so I hope | somebody could illuminate it for me. | shimon wrote: | I studied CS and now work in software systems for biomedical | research. It's difficult to overstate how different the fields | are, so I don't entirely agree with this statement. But I do | agree there are going to be lots and lots of huge discoveries | in biology in the 21st century. | | The main difference is that CS attempts to generate and study | complex systems built from well-understood components, whereas | biology attempts to understand and manipulate systems that | evolved naturally over eons. | | Imagine dropping a fully functional internet-connected Google | Home Hub into 1960-era humanity and asking them to figure out | how it works so they modify it to sound like Walter Cronkite. | There are thousands of problems on this order of complexity in | biology. It's wild. | tyre wrote: | think of the tech debt in our legacy codebase | elevaet wrote: | 3.7 billion years of refactoring has kept it pretty clean | and functional. We'll need to do a shit ton of unit and | integration testing before we commit changes. | jazzyjackson wrote: | This is basically chaos engineering applied the the genome | | It doesn't say "this gene has this outcome" so much as it says | "this outcome fails when this byte of data is missing" | throwawaycities wrote: | About 18-24months ago I went through a phase of listening to | geneticists talks/conferences/podcasts for an hour or two a day | during long runs, it's so far outside my wheelhouse I'm | probably mixing things up, but I thought I recalled cutting | edge experiments using synthetic cells to create artificial | life (a worm perhaps with a relatively simple DNA, maybe even a | modified DNA further simplifying the genome to the furthest | extent possible still resulting in life) with one of the goals | of understanding the exact functions of all the genes in this | "simple" DNA. Again I'm probably mixing up multiple discussions | and studies into one, but I would have been very surprised if | the function of every single gene in the human genome was known | and understood, as suggested by the title. | tablespoon wrote: | > I recalled cutting edge experiments using synthetic cells | to create artificial life (a worm perhaps with a relatively | simple DNA, maybe even a modified DNA further simplifying the | genome to the furthest extent possible still resulting in | life) | | A worm seems super-complex for something like that. I'd guess | they'd actually use a bacterium. | dekhn wrote: | I worked with mycoplasma genitalium which is a "minimal" | organism- an extremely small number of genes, nearly all of | which appear to be absolutely required for viability. It's | sort of a unit test for model biology, except it grows so | slowly it's more like an integration test in terms of | performance. | | You are probably referring to Mycoplasma genitalium JCVI-1.0 | ( (see https://en.wikipedia.org/wiki/Mycoplasma_genitalium) | as worms are too complex to be minimialized | | See also | https://en.wikipedia.org/wiki/Mycoplasma_laboratorium | | The work in this area is quite extraordinary, but typically | gets much less attention than _anything_ that works with | human genomes. | gilleain wrote: | Hmm wonder how Craig Venter is getting along with his | project. He was making a lot of noise about it a few years | ago. | | Seems like he sold a company in April of this year to the | University of California. | lgas wrote: | Maybe https://en.wikipedia.org/wiki/Caenorhabditis_elegans# | Use_as_... ? | dekhn wrote: | c. elegans is much more complicated. It has the advantage | of eutely, but it's awfully complex for minimalist | studies. | mariebks wrote: | Can you link to some of your favorite | talks/conferences/podcasts? Thanks! | bigbillheck wrote: | "This Week in Virology": https://www.microbe.tv and sister | podcasts. | yellowcake0 wrote: | Well, depending on how broad your definition of life is, | viruses have the most stripped down genomes of all. In the | smallest viruses, with genomes of just under 10kb in length, | nearly every basepair is dedicated to either infection or | replication. In fact, they are often so compact that open | reading frames are interleaved, in order to provide more | functionality without increasing size. | | Scientists often refer to viruses as "obligate", in order to | sidestep the question of what is life, as most have no | interest in the topics which occupy philosophers. In any | case, they are non-cell based, for whatever that is worth. I | imagine in a non-hostile environment, even the infection | functional would be shed, and you would be left with just | replication, which is the fundamental component beyond which | no further reduction in complexity can be made. | bigbillheck wrote: | > viruses have the most stripped down genomes of all | | Giant viruses can have over 1M basepairs, substantially | larger than a bacteria such as Mycoplasma genitalium, with | substantial functionality (pretty much everything except | the ribosome in at least some of them: | https://www.virology.ws/2018/03/08/only-the-ribosome-is- | lack...) | afterburner wrote: | > I imagine in a non-hostile environment, even the | infection functional would be shed, and you would be left | with just replication | | A virus replicates by infecting another cell and taking | over its actual replication infrastructure, so getting rid | of infection gets rid of replication too. | ethbr0 wrote: | Minimal genome - | https://en.m.wikipedia.org/wiki/Minimal_genome | | I thought some work on it made HN, but can't seem to find the | article, about a research group that was continuing to strip | things out and then test viability. | yellowcake0 wrote: | You may also be interested in the Yeast 2.0 project, | | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894084/ | | which is an attempt to redesign the genome of the model | organism S. cerevisiae, i.e. standardize codons, remove junk | DNA, etc. | [deleted] | pishpash wrote: | It's kind of a dead end I feel. It can turn out that everything | is used for everything. It's not designed so there is probably | no clean decomposition nor is it necessary. | david_l_lin wrote: | Not really? | | It says that some genes result in the same outcome when knocked | out as other genes, and identifies novel genes that putatively | participate in the same pathways as others. This helps get at | the potential function of genes without known functions. | jazzyjackson wrote: | > It says that some genes result in the same outcome when | knocked out as other genes | | a very useful map to make, but I don't see that this | contradicts my comment - both genes in this case are | dependencies to the outcome, without either of them, the | outcome fails | | this does not sound to me like we know the "function" of | these genes, only that they're nessary for each phenotype | | not to knock the research, just trying to make sense of what | they're really mapping, in my own language of computer code | (i suppose "function" has a different connotation in | genetics) | david_l_lin wrote: | > "this outcome fails when this byte of data is missing" | | The outcomes here are not failures, they are measurable | phenotypic differences, which they use to group genes into | phenotypic outcomes. The typical "knockout -> failure to | perform a function" is not what's being measured here. | timy2shoes wrote: | > this does not sound to me like we know the "function" of | these genes, only that they're nessary for each phenotype | | But they're not even measuring the phenotype. They're using | the transciptional signature as a substitute for | phenotype/cell function (i.e. the bag of RNA model). This | is a poor substitute if you try to apply this to practical | applications such as cell engineering. Let's say I perturb | a cell to match it's transcriptional signature to that of a | neuron. Does that make it a neuron? Not if it doesn't | function like a neuron. | twic wrote: | I think this is a really important point. With a few | exceptions (like the neat implied aneuploidy assay), they | haven't measured an outcome or phenotype for the genes. | They have measured the impact on transcription (well, | mRNA levels, via transcription or some other effect). | That is an extremely useful dataset, but it's not enough | to say what the phenotypic effect of knocking out any | given gene is, much less what the actual mechanistic | function of the gene product is. | | It's also important to note that there are loads of genes | whose effects are not mediated by changes in mRNA levels. | If you knock out Arp2, a cell can't move properly, | because Arp2 is involved in assembling cytoskeletal | structures needed to do that, but you probably won't be | able to tell that by looking at the cell's mRNA. | dekhn wrote: | So, people do this a lot and frequently make mistakes. For | example, when you knock out a gene, you also damage any | overlapping genes (yes, genes can overlap). most studies | don't pay attention to the damage they do to overlapping | genes. | | The underlying physical model for how gene products interact | to make phenotypes ends up being so hopelessly complex and | latent that most conclusions in this area end up being | "sufficient, but not necessary" instead of "necessary, but | not sufficient" | ramraj07 wrote: | Not sure if you're doing it a service or disservice calling it | chaos engineering: at best it's related. If you want to figure | out what a complex system does where you have no ability to | "see", the only tool you have most of the time is to knock out | individual components and see what happens. | | As you might guess this is generally a blunt tool which can | help you get to the first 30% of the understanding of the | system but minimal extra data after that. The majority of genes | discovered in this study would either be already known players | in those pathways or unknown genes that would already have been | guessed to play a role. | | Until one of these massive screens tells us what the major | vault protein complex does they should all be honest about what | they are which Imo is just a minor addition. | Victerius wrote: | Designer babies incoming. | | Turn off the genes that would make my child below 6'5 in | adulthood, turn off the genes that wouldn't make him naturally | muscular, turn off the genes that would give him an average | intelligence, etc. | | $10M + options. Payable in monthly installments. | zen_1 wrote: | Turn on the Myostatin inhibitors! | WitCanStain wrote: | A new genetic aristocracy. Great. | elif wrote: | Yea human culture will find a new level of 'basic' combined | with an inferred and understood if not blatantly codified | position of social superiority... Sounds more like twilight | zone than social progress to me. | cronix wrote: | What do you think they would choose if they had the option | for gender, orientation and sexual preference? | Victerius wrote: | Most wealthy couples with the means to afford designer | babies would probably want heterosexual children. Gender | would be left at their discretion. | mcculley wrote: | Not just wealthy couples. Most parents want their | children to be heterosexual and bear them grandchildren. | Having successfully procreated, they are more likely to | have natalist genes and inclinations. | lajamerr wrote: | Why would they need to be heterosexual to successfully | procreate. | | If the future is designer babies/baby incubation pods. It | doesn't matter what sexual orientation the kid is. The | parent would have a designer baby, then why would the | child eventually not have a designer baby as well? | DrudgeCorporate wrote: | You will always need an Egg or Sperm depending on which | is missing in the relationship. Also, one of the parents | would not have genetic code in the offspring since you | can't splice two eggs/sperm together as far as I know. | blamestross wrote: | We already selectively breed for natalists and look how | that turns out. It actually makes an argument that | genetic predisposition to natalism is currently rather | weak and it is mostly memetic predisposition in practice. | InitialLastName wrote: | The demographic trends we're seeing now (declining birth | rates for affluent people in the developed world) could | be due to our natalism level being mis-calibrated for our | current circumstances. | | It's good evolutionary strategy to reduce the birth rate | to compensate for successful reproduction (i.e. more | pregnancies that result in offspring that reach child- | rearing age themselves), as otherwise populations will | explode beyond the carrying capacity of the environment | (or pay more of the fixed resource costs of raising | children than is necessary). | | What we see now, however, is that in situations where | both pre-adult and maternal mortality rates are | _exceedingly_ low (such as has been the case for the last | ~4-5 generations in the developed world), the strategy | undershoots the replacement rate. | fgkramer wrote: | We just need to see Gattaca to be horrified at the results of | such experiment. | sneak wrote: | I have seen Gattaca and don't find human genetic | engineering to be horrific. It's cool and exciting that | people will be able to have better children than they would | have otherwise. | tablespoon wrote: | > I have seen Gattaca and don't find human genetic | engineering to be horrific. It's cool and exciting that | people will be able to have better children than they | would have otherwise. | | Did you even pay attention to the movie? The horrific | aspect was the human genetic engineering led 1) to the | the _un_ engineered to be turned into an underclass that | was blatantly and unfairly discriminated against, and 2) | that same discrimination would be turned against the | engineered if they had an accident that caused them to | fall short of the expected perfection. | | I have little doubt that the reality of genetic | engineering (that was is effective as that depicted) | would rhyme with that movie. It's also nearly certain | that any such technology would not be distributed in an | egalitarian way, so the sentiment should be more like | "it's cool and exciting that [well off] people will be | able to have [genetically superior] children than [the | plebs]." | nescioquid wrote: | > It's cool and exciting that people will be able to have | better children than they would have otherwise. | | You know, I used to be wary of eugenics, but when you put | in that light, yeah, I'm kinda tired of putting up with | everyone's crap kids. If you could make them be quiet, | sit still, and do as told, that would be a fantastic | achievement! Oh, and maybe make them smarter, too. Ever | try to actually _talk_ to one (the newer ones are really | pretty stupid)? | sneak wrote: | Genetic engineering of one's own children is not | eugenics. It's not even close. | | Most of my friends' children are smart. The ones not | raised in the USA are generally well-behaved. Your sample | size may need to be increased. | rowanG077 wrote: | Honestly I love this future. There are so many bad traits | humans have that would help everyone a great deal if they | would be eliminated. | elif wrote: | Consider that idea's other subscribers in history, the ones | utilizing that exact rationality... Are you in good | company? | rowanG077 wrote: | I think so. Alexander Graham Bell, Helen Keller, Winston | Churchill, Plato and there are countless more. Just | because we didn't have the technology to implement it | humanely in the past doesn't mean it can't be done in the | future. | | In fact. I would consider a society, that has the | capability to noninvasively eliminate for example sickle | cell anemia or Huntingtons and doesn't because some | people one hundred years ago did horrible things, | barbaric. | atlasunshrugged wrote: | $10M+ now and then in 20 years figure out that changing that | gene sequence creates a dramatically higher likelihood for | Alzheimer's or infertility. I personally am not against the | modification of humans in practice, I think it's an | interesting opportunity for humans to take control over the | evolutionary process and optimize ourselves for the world we | live in now (and future ones), e.g., what if we could | minimize the amount of sleep needed, or our tolerance to heat | so climate effects were somewhat mitigated, or so our bodies | were less affected with long periods in space? The tie-in of | capitalism to it creates a weird dynamic but I'm not sure I | see an obvious better solution unless we want to outlaw | everything except for government approved research and let | the ideas be at the whims of whatever bureaucrat or political | appointee happens to be in charge at the time. | MontyCarloHall wrote: | >$10M+ now and then in 20 years figure out that changing | that gene sequence creates a dramatically higher likelihood | for Alzheimer's or infertility | | Not only that, but any genes that are not selected against | (e.g. your Alzheimer's example, which occurs after | reproductive age) are now permanently circulating in the | population, with absolutely zero (humane) way of ever | removing them. | dekhn wrote: | In the short term, a lot of gene therapy focuses on the set | of diseases where the repair really does seem to be "change | this one base" and there are no side effects due to | complex, unknown gene interactions or other unexpected | phenomena. m And nearly all of it (I haven't looked at the | details in a while) is just treatment (IE, injections of a | gene therapy in a post-birth individual), rather than | preventive by germline manipulation, which IMHO | | It's likely that for the time being we'll only use gene | therapy for things which are recognized as devastating | diseases and the treatment is extremely reliable; germline | modification for enhanced attributes in typical individuals | is still a fairly out-there concept that would probably get | panned in the media. | daniel-cussen wrote: | This already is what happens with sexual selection. That is | the purpose of sexual selection from the point of view of | genetic integrity. People are designing their babies every | time they have sex. There's huge amounts of money involved | there too. And like how do I know the geneticist isn't | slipping his own in-born DNA in my place, like that fertility | doctor did or that criminal inseminator who broke into | poorly-guarded sperm banks and substituted his sperm for that | of astronauts with Nobel Prizes? Had like 660 kids that way. | | Like there good reasons to do this are, OK genetic | malformation, ie osteogenesis imperfecta, that's a SNIP, | totally. Or you were raped, want to punish that rapist by | making the egg have even less genes in common with him than | it would ordinarily, making his rape counterproductive | genetically. Another good reason, defensible. Or you want to | protect rare alleles, considering weaknesses to be strengths, | this is like a left-handed man marrying a left-handed woman, | or freckles (I think something about freckles make children | hate them til they're 19, rare exceptions, not even the | iconic Lindsay Lohan accepted her own freckles). Preserving | their identity and diversity. Don't pass laws as much as | using judgment to decide, individually and collectively, what | the future will be. Talk and think instead of setting up | magic words for lawyers to copy-paste--an isomorphic problem | to genetic design. | | No fucking blind copy-paste, don't use copy-paste with your | copy paste to copy-paste yourself. | ineptech wrote: | This doesn't really pass the sniff test; if there were any | easy one-gene changes that resulted in unambiguously better | results, it's highly likely that we'd all have them already. | elevaet wrote: | Well, these aren't unambiguously "better results", not in a | biological sense. Just better in terms of what our culture | values, and not necessarily better survival and | reproduction. | dharma1 wrote: | memes manipulating genes | rootsudo wrote: | This is cool, so in laymans terms - you can disable the bad | "genes" and just express/enable/push the "good ones." | | So how do we define what is a bad gene? If we use crispr, can we | turn it off on an actual, live, aging human being or only before | they're "born" or such? | | Is there a good resource/book that gets someone from zero to a | basic biological understanding and background of this and above? | I _really_ have no idea, nor do I know who to ask. :( | cvccvroomvroom wrote: | Not in the field. | | Q: How can the human genome be "mapped" without sampling and | sequencing genetic material from millions of individuals? Is it a | sequencing of one individual? | mdaniel wrote: | > New CRISPR-based map(ping process) ties every human gene to its | function | | Maybe it's because I'm not in that industry, but I was looking | for a graphical gizmo that I could click on a gene and see | functions but they mean "map" in its functional programming term | | Although clicking through the first link does say "Interactive | Website under construction..." so maybe this was just submitted | too early or something | dekhn wrote: | Here's a link to the gene they mention: C7orf26 | https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtMod... | | To understand its function, it has its own wikipedia page(!) | https://en.wikipedia.org/wiki/C7orf26 It's one of the remaining | proteins whose "function" (to the extent that proteins can be | said to have a "function") has not been reliably determined. | | There are sites for protein function, my favorite is Uniprot: | https://www.uniprot.org/uniprot/Q96N11 | | as you can see, they don't really know what it does: "Probable | component of the Integrator (INT) complex, a complex involved | in the small nuclear RNAs (snRNA) U1 and U2 transcription and | in their 3'-box-dependent processing.". | | The integrator complex is an important bit of machinery that | helps transcript DNA to RNA on its path to protein expression: | https://www.embl.org/news/science/at-the-core-of-the-integra... | | In general, data presentation in biology is a pretty mixed bag. | The field never attracted the level of UX investment that you | see at ad-driven companies. | lysozyme wrote: | That's true, software for biology tends to be terribly, | almost comically bad, with one-off file formats, brittle data | interchange, and impossible-to-maintain code being the norm. | With user interface and ergonomics being the most neglected | aspect. Why do you think that is? | | Surely there is plenty of money in biology these days to hire | a good designers to design good user experiences. Surely | better user experience for biology software would lead to | better understanding of biological systems and better | outcomes in bioengineering. | | Where are the polished, powerful design tools for biology | like those that exist for other fields like online | advertising that routinely process and distill huge amounts | of lightly-structured data? | caycep wrote: | it seems like that is a whole other skillset vs. biology | graduate students...I know the Allen Institute employs data vis | people to write visualisation tools like this in d3/react or | whatever the web api du jour is, but they are separate from the | science folks | grej wrote: | Another cool thing, their paper mentions that, "The specific | implementation is based on the python package torch-two-sample, | modified to use numba for improved performance." ( | https://www.cell.com/action/showPdf?pii=S0092-8674%2822%2900... ) | | If you haven't checked out the numba package, definitely worth a | look for custom numerical computing in Python! | | disclosure - have made a small contribution to the package. | atlasunshrugged wrote: | Anyone know where the state of the art is happening in applied | 'designer baby' tech? I feel like there hasn't been much news | since the arrest of the scientist who claimed to be the first to | change the genes of live kids but I'm shocked there aren't some | people out there pushing the envelope on this (and/or | commercializing it). | cauthon wrote: | Never underestimate MIT's ability to oversell itself. | | (EDIT: see below, this is directed at the press release, which I | perceive to be overstating the achievements presented in the | paper, not the quality of the paper itself) | warent wrote: | Care to elaborate? This just seems like an empty criticism | without any value or substance | cauthon wrote: | Sure. A genome-wide perturb-seq experiment is a huge (and | expensive) technical accomplishment, but the authors did not | "map every human gene to its function". (Nor did they claim | to, it's press release hyperbole.) | | One, there's ~20k protein-coding genes in the human genome, | and they screened ~10k, analyzing about 2k (fig 2a). | | Two, all the functional annotation is based off transcription | profiles. They essentially looked for clusters of genes with | correlated expression, and assigned function based on genes | with previous annotations (fig 2d, S4). | | It's a good resource, but there's a lot more molecular work | to be done to validate the function of these genes. | timy2shoes wrote: | > Two, all the functional annotation is based off | transcription profiles. They essentially looked for | clusters of genes with correlated expression, and assigned | function based on genes with previous annotations | | This is an important point, because if you've ever worked | with single cell data you'll know that the transcriptional | profile is extremely noisy and your transcriptional profile | to cell type map has many researcher degrees of freedom. I | heard a story about a paper early in the single cell work | that started with 53 cell types and after review ended up | with 37 cell types. Are those true cell types? Did the | experimenters validate that those cell types all performed | different functions? Well, of course not. That's way too | much work. | | Then add on technological biases, which make mapping | between technologies difficult. I say this because they | used a new sequencing technology that appears to have | homopolymer bias | (https://twitter.com/lpachter/status/1533875723995185153), | which will bias the gene quantification. | cauthon wrote: | > I say this because they used a new sequencing | technology that appears to have homopolymer bias (https:/ | /twitter.com/lpachter/status/1533875723995185153), which | will bias the gene quantification. | | I believe they used Illumina for the results presented in | the main text and then re-sequenced with Ultima and | replicated a subset of the analyses (fig s13). The Ultima | proof-of-concept didn't appear to be relevant to the main | study/conclusions | dekhn wrote: | Is there a way to get the parent comment unflagged? The | response from the commenter shows they have a lot to | contribute, technically speaking. | cauthon wrote: | Thanks. I'll admit the first comment didn't contribute much | and apologize for not including my thoughts from the | follow-up. I just don't care for these sorts of hyperbolic | press releases. | | It's part of the game, the big players are as good at sales | as they are at science, but I've never been a fan of it. | dekhn wrote: | Useful book that any starting professor should | understand, even if they don't want to admit they are | playing a game. science-by-press-release is a technique | to master if you want to both maximize the impact of your | work, and get tenure. | | https://www.amazon.com/Winning-Games-Scientists-Play- | Sinderm... | Noumenon72 wrote: | I have `showdead` turned on in my profile, and I saw this | whole comment chain. Will people with it turned off still | see the replies? | wolverine876 wrote: | You can click 'vouch'. | dekhn wrote: | Thanks, I didn't realize you had to click through to the | comment to see that. | coryfklein wrote: | Wait do we even know that every human gene has a 1:1 mapping to a | function in the body? I think the code analogy to this would be | trying to map "C++ if statements" to a particular feature in your | product. I'd expect something as complicated as the genome would | have a much richer and complicated interaction with biological | feature expression. | | I'm probably simply misunderstanding; maybe Weissman's data is a | 1:N mapping? | shpongled wrote: | We already know that many genes have more than one function | (especially when you consider that one gene can produce many | protein products) | elif wrote: | I think mpeg encoding would be a better demonstrative than | code... | | Where data is lost, details are lost, but the end result still | typically renders into something recognizable. If you lose an | iframe, you end up with a more serious deformity. Whereas code | either does exactly what it says or does nothing at all, and | knocking out a single statement is almost certain to break | everything. | astrange wrote: | This kind of shallow presentation is common for genetics; | compare reporting genetic traits by SNPs and implying the SNPs | "cause" them, which is like diffing two versions of a program | and saying X new feature happens because there's a letter 'n' | in one program and not the other. | axg11 wrote: | There's not any type of mapping and this is what makes biology | so difficult to study and understand. One gene can affect | anywhere from zero other genes to every single gene. We also | need to account for effects at every level of the central dogma | of biology. Knockout of a gene can affect genetics, RNA, | protein, and much more we don't even know about yet. The other | underestimated complicating factor is that biology is very | nonlinear. A 10% increase in gene expression could lead to no | resulting effect, whereas an 11% increase in expression could | upregulate downstream genes by 1000x. | geysersam wrote: | I'm not a biologist. Still, do genes really have "functions"? | Guess some have, such as producing an enzyme to break down a | particular kind of suger. But that this would be the case for | _every human gene_ sounds unlikely to me. | projektfu wrote: | A gene is a DNA (or RNA) sequence that codes for some protein | or RNA product. There are other functional sequences in DNA but | they're not called genes. | | https://en.wikipedia.org/wiki/Gene?wprov=sfti1 | dekhn wrote: | For your last sentence: that's right, to get any press | attention today you have to basically say you've solved all | cancer or done something pan-genomic, in a way that massively | overstates the importance of the specific result and its impact | on health care delivery. | | That said, Jonathan Weissman is a great guy who has pushed the | field forward and the techniques they are using really are | powerful. | panabee wrote: | thanks for all your comments and insights. can you recommend | other people to follow on the leading edge of integrating | technology and biology? | commandlinefan wrote: | > do genes really have "functions"? | | Makes me think of Douglas Hofstatder's "grandma neuron": | https://www.livescience.com/grandmother-neurons-discovery.ht... | radicality wrote: | His explanation in GEB of how genes, DNA, and RNA function | was probably the clearest one I've ever read. It's been a | while and I forgot the details, but reading his analogies | made everything click at the time. Maybe it's time to re-read | GEB. | david_l_lin wrote: | All genes have a function. This paper helps us understand genes | of unknown function (which is a LOT of them). | | Some of these functions are not intuitive: maybe they regulate | the function of another protein, maybe they only function in | the context of a particular stressor, etc. You can think of | nearly unlimited scenarios to apply and you start to understand | the complexity of understanding how a gene functions. | dekhn wrote: | "All genes have a function" <- this is a generalist statement | that is wrong in its specifics, but also raises semantic | question of what "function" actually means. | pfisherman wrote: | "All genes have a function" is analogous to saying, "All | particles play a role in our physical reality". This should | be uncontroversial. | dekhn wrote: | This is a bit of a semantic argument, but gene function | is a fairly nebulous term. The essence of what I am | saying is that there may be proteins that currently have | no actual function, aren't under functional selection, | yet are duplicated, transcribed, and expressed (not just | pseudogenes). | | Function is a rabbit hole. Biologists get in big | arguments about the semantics of this all the time | (http://cryptogenomicon.org/encode-says-what.html). I | don't really care. I care about the minimal set of | necessary proteins for a model organism to exist and | reproduce in a media-rich environment. And, whether there | are actually subsets of mutually compensatory groups of | proteins instead of a single minimal set. | | Protein function is one of those things that, at first, | seems really simple to define, but the further you go | down the rabbit hole, the more complicated it gets, until | it's fractally complex and you realize that not only does | the exception prove the rule, it's all exceptions. | | See also: | https://en.wikipedia.org/wiki/Enzyme_promiscuity | axg11 wrote: | > All genes have a function. | | For the benefit of readers unfamiliar with the field: this is | wrong. | | You can show this experimentally. Construct a gene that | produces a non-human protein and introduce this to a human | cell/genome. That gene would not have a "function" but still | exists in the genome. This is actually happening all the | time. Some viruses integrate their genomes when infecting | cells. Viral integration is one of the factors that shapes | genome evolution. | eurasiantiger wrote: | All human proteins are encoded in genes. | | https://en.wikipedia.org/wiki/Category:Human_proteins | [deleted] | Obi_Juan_Kenobi wrote: | A gene is essentially defined as having a gene product, either | an RNA or protein. So yes, all genes are functional. | | Genes that aren't translated into protein sequences (noncoding | genes) can create structural RNAs as with Ribosomes, microRNAs | that have regulatory functions, etc. | | There are lots of non-gene genetic elements that do things, | though. Many are involved in gene regulation, affecting the | transcription rates of nearby loci through a variety of | mechanisms. There are also vast swaths of inactivated | transposons, retroviruses, and other repetitive genetic | sequence. | imchillyb wrote: | This is akin to taking an automobile apart piece-by-piece, not to | determine its function but just to figure out if the automobile | fails substantially by removing say a taillight, dome light, dash | light, or wiper delay fuse. | | The car's not gonna fail for each piece, it'll take forever to | determine what pieces are absolutely necessary, and it doesn't | tell ya shit about what the pieces functions are. | | Neat, but ultimately inefficient and exceedingly limited in | necessary detail to make the claim in the article's title. | [deleted] | throwawayarnty wrote: | One model of how science progresses is a few pioneers breaking | new ground and then everyone else rushing in to pick up low | hanging fruit in the new field. | | Looks like Weissman lab has consistently been breaking new ground | over and over again. Extremely impressive and very few labs in | the world have such a track record. | bryans wrote: | An article from MIT:TR in the early 2000s always stuck with me as | an example of how intricate and interconnected genes really are. | Researchers using fruit flies found one born with white eyes, and | they narrowed the mutation to a specific gene. They were able to | modify it in vivo to reliably produce white eyes, but the change | had an unexpected second outcome, which was that white-eyed males | would only attempt to mate with other males. | | Years later, there was a group who cited that fruit fly paper | when they proposed the same methodology to control mosquito | populations, but I'm not sure if they ever recreated the male | preference. The mosquito gene editing did pan out, but the method | is different in that it doesn't allow females to survive, while | males will go on to mate with other non-edited populations and | spread the female-killing gene. | jmyeet wrote: | This is really amazing. | | Of course I was aware of the Human Genome Project and mapping DNA | in general. I was also aware that figuring out all the proteins | in a cell and what they do is a whole other problem. | | I didn't realize they'd made this much progress. It's not | complete obviously but being able to figure out gene expression | is a _massive_ step forward. The ability to switch off genes | (this is where the CRISPR editing comes in) and seeing what | changes is just astounding (there was an example of chromosome | segregation). | | It's known that certain proteins mediate certain processes where | the presence of that protein or the absence of it can lead to a | condition or disease. The potential impact here for treating | genetic disorders I think cannot be overstated. | | Between this an the technology behind mRNA vaccines, I really | wonder if the 21st century will lead to the effective elimination | of many diseases. | tandr wrote: | > Between this an the technology behind mRNA vaccines, I really | wonder if the 21st century will lead to the effective | elimination of many diseases. | | And, due to errors and human mistakes, possible creation of | some new, or old-but-improved ones... | jjtheblunt wrote: | > The ability to switch off genes (this is where the CRISPR | editing comes in) | | i think your wording is ambiguous : CRISPR can edit the | sequence, but "switch off" has an association with methylation | of items in the sequence, orthogonal to the sequence itself. | Obi_Juan_Kenobi wrote: | You misunderstand. | | We've being doing genetics for decades. Molecular biology | without mutant studies wouldn't exist. It's the foundation of | the field. | | All this is is a difference in scale. But it is a very crude | tool; really understanding gene function involves studying it | in relevant contexts. Looking at cells in tissue culture can | give you some ideas or hints about how it functions, but the | critical insight might require certain cell types or gene | regulatory environments. | | What data like these do is inform hypothesis generation and | refine the interpretation of genomic data. It is important | work, but does not replace doing actual biology. | | What you're talking about is essentially saying we just | invented molecular biology. Which is obviously not the case. | Filligree wrote: | > I didn't realize they'd made this much progress. It's not | complete obviously but being able to figure out gene expression | is a massive step forward. The ability to switch off genes | (this is where the CRISPR editing comes in) and seeing what | changes is just astounding (there was an example of chromosome | segregation). | | The protein folding problem was solved earlier this year. You | can expect a lot more coming in this vein... interesting times. | dekhn wrote: | the protein structure prediction problem was solved, not | protein folding. Different field. Also, it wasn't really much | "solved", so much as prediction got as good as the metric | used to compare the predictions to reality, so we can't | really say for sure whether the predictions are better than | golden labels or not. | hirako2000 wrote: | The 21st centry may lead to the definitive elimination of | humans, of desease i can only imagine their numbers going up, | not down. | | "that's where CRISPR editing comes in". To edit the DNA of | congeniality diseased people? I doubt the business will focus | primarily on this category of patients, unfortunately. but I | still hope the worst will be avoided when/if using this tech | kind of tech. | BurningFrog wrote: | I suspect FDA regulations will have to be redesigned a lot to | make most DNA editing treatments economically possible. | hirako2000 wrote: | If they approved the sort of recent treatment they | approved, for that scale of deployment (billions of | individuals within a year) it wouldn't surprise me they | will approve anything, given enough lobbying. No worry to | have with FDA becoming an obstacle. ___________________________________________________________________ (page generated 2022-06-10 23:00 UTC)